Nutritional Biomarkers for the Prediction of Response to Anti-TNF-α Therapy in Crohn's Disease: New Tools for New Approaches

Crohn’s disease (CD) is a chronic disorder of the digestive tract characterized by an uncontrolled immune-mediated inflammatory response in genetically predisposed individuals exposed to environmental risk factors. Although diet has been identified as one of the major environmental risk factors, the role of nutrients in the clinical management of CD patients has not yet been fully investigated. In this prospective observational study, fifty-four patients diagnosed with active Crohn’s disease and undergoing anti-TNF-α biological therapy were enrolled and subjected to nutrient intake analysis through a daily food diary. Their nutrient intake and blood values were analyzed before and after 6 months of biological therapy. After 6 months of anti-TNF-α, four patients dropped out of the study, leaving 29 patients in clinical remission and 21 still with active disease that remained the same. The aim of this study was to identify nutrients whose intake or blood values may be associated with patients’ responses to biological therapy. In the diet, patients remaining with active CD showed very similar nutrient dietary intake compared to patients achieving remission except for a trend for lower starting zinc intake, below the reference value. In the blood, instead, patients who did not respond to biological therapy showed significantly lower plasma values of iron and taurine before starting biological anti-TNF-α treatmen

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Palmitoylethanolamide (PEA) for Prevention of Gastroesophageal Inflammation: Insights from In Vitro Models

Gastroesophageal reflux disease (GERD) is a digestive disorder that can lead to chronic mucosal damage, causing esophagitis, Barrett’s esophagus and esophageal cancer. GERD currently affects about 13% of the world’s population and represent a major public health concern due to the increasing prevalence and incidence. The aim of this study was to explore complementary strategies for GERD management based the natural compound palmitoylethanolamide (PEA), alone or associated with plant extracts with demonstrated anti-GERD activity (Zingiber officinale, Musa × paradisiaca, Opuntia ficus-indica and Olea europaea). For this purpose, two in vitro models based on the esophageal mucosa CP-B cell line were chosen. The first one was based on the exposure of esophageal cells to HCl, while the second one was based on lipopolysaccharide (LPS) treatment to cause a strong inflammatory cell response. Inflammation induced was assessed using a Luminex® assay, measuring the secretion of IL-1β, IL-6, IL-10, IL-8 and TNF-α. Results obtained demonstrate that PEA strongly decreased the inflammatory response elicited by HCl exposure. Moreover, the effect of PEA was enhanced by the presence of natural extracts of Zingiber officinale, Musa × paradisiaca, Opuntia ficus-indica and Olea europaea. PEA should be considered as an anti-GERD natural compound of interest

COVID-19 in IBD: The experience of a single tertiary IBD center

Background: Italy has been one of the most affected countries in the world by COVID-19. There has been increasing concern regarding the impact of COVID-19 on patients with inflammatory bowel disease (IBD), particularly in patients treated with immunosuppressants or biologics. The aim of our study is to understand the incidence of COVID-19 in a large cohort of patients with IBD. Furthermore, we analyzed possible risk factors for infection and severity of COVID-19. Methods: This was an observational study evaluating the impact of COVID-19 on IBD patients in a single tertiary center. A 23 multiple-choice-question anonymous survey was administered to 1200 patients with IBD between March 10th and June 10th 2020. Results: 1158 questionnaires were analyzed. The majority of patients had Crohn’s disease (CD) (60%) and most of them were in clinical remission. Among the 26 patients (2.2%) who tested positive for COVID- 19, only 5 (3CD) were on biological treatment and none required hospitalization. Two patients died and were on treatment with mesalazine only. Of the 1158 patients, 521 were on biological therapy, which was discontinued in 85 (16.3%) and delayed in 195 patients (37.4%). A worsening of IBD symptoms was observed in 200 patients on biological therapy (38.4%). Most of these patients, 189 (94.5%), had stopped or delayed biological treatment, while 11 (5.5%) had continued their therapy regularly ( p < 0.001). Conclusions: Our data are in line with the current literature and confirm a higher incidence compared to the general population. Biological therapy for IBD seems to not be a risk factor for infection and should not be discontinued in order to avoid IBD relapse

Trends and safety of bariatric revisional surgery in Italy: multicenter, prospective, observational study

Background: Revisional bariatric surgery (RBS) represents a further solution for patients who experience inadequate weight loss (IWL) following primary bariatric surgery (BS) or significant weight regain (WR) following initial satisfactory response. RBS guidelines are lacking; however, an increased trend in further BS offerings has been reported recently. Objective: Analyze trend, mortality, complication, readmission, and reoperation rates for any reason at 30 days after RBS in Italy. Setting: Ten Italian high-volume BS centers (university hospitals and private centers). Methods: Prospective, observational, multicenter study enrolling patients undergoing RBS between October 1, 2021, and March 31, 2022, registering reasons for RBS, technique, mortality, intraoperative and perioperative complications, readmissions, and reinterventions for any reason. Patients undergoing RBS during the same calendar interval in 2016-2020 were considered control patients. Results: A total of 220 patients were enrolled and compared with 560 control-group patients. Mortality was .45% versus .35% (n.s), with an overall mortality of .25%, while open surgery or conversion to open surgery was registered in 1%. No difference was found for mortality, morbidity, complications, readmission (1.3%), and reoperation rates (2.2%). IWL/WR was the most frequent cause, followed by gastroesophageal reflux disease; Roux-en-Y gastric bypass was the most used revisional procedure (56%). Sleeve gastrectomy was the most revised procedure in the study group, while gastric banding was the most revised in the control group. RBS represents up to 9% of the total BS in the Italian participating centers. Conclusions: Laparoscopy represents the standard approach for RBS, which appears safe. Current Italian trends show a shift toward sleeve gastrectomy being the most revised procedure and Roux-en-Y gastric bypass being the most frequent revisional procedure

A Mediterranean Dietary Intervention in Female Carriers of BRCA Mutations: Results from an Italian Prospective Randomized Controlled Trial

Background: Women carriers of BRCA1/2 mutations face a high lifetime risk (penetrance) of developing breast and/or ovarian cancer. Insulin-like growth factor I (IGF-I), body weight and markers of insulin resistance affect BRCA penetrance. We conducted a multicenter prospective two-armed (1:1) randomized controlled trial (NCT03066856) to investigate whether a Mediterranean dietary intervention with moderate protein restriction reduces IGF-I and other metabolic modulators of BRCA penetrance. Methods: BRCA carriers, with or without a previous cancer, aged 18–70 years and without metastases were randomly assigned to an active dietary intervention group (IG) or to a control group (CG). The primary endpoint of the intervention was the IGF-I reduction. Results: 416 women (216 in the IG and 200 in the CG) concluded the six-month dietary intervention. The IG showed significantly lowered serum levels of IGF-I (−11.3 ng/mL versus −1.3 ng/mL, p = 0.02), weight (−1.5 Kg versus −0.5 Kg, p &lt; 0.001), waist circumference (−2 cm versus −0.7 cm, p = 0.01), hip circumference (−1.6 cm versus −0.5 cm, p = 0.01), total cholesterol (−10.2 mg/dL versus −3.6 mg/dL, p = 0.04) and triglycerides (−8.7 mg/dL versus + 5.5 mg/dL, p = 0.01) with respect to the CG. Conclusions: A Mediterranean dietary intervention with moderate protein restriction is effective in reducing IGF-I and other potential modulators of BRCA penetrance.</jats:p

A Mediterranean Dietary Intervention in Female Carriers of BRCA Mutations: Results from an Italian Prospective Randomized Controlled Trial

Background: Women carriers of BRCA1/2 mutations face a high lifetime risk (penetrance) of developing breast and/or ovarian cancer. Insulin-like growth factor I (IGF-I), body weight and markers of insulin resistance affect BRCA penetrance. We conducted a multicenter prospective two-armed (1:1) randomized controlled trial (NCT03066856) to investigate whether a Mediterranean dietary intervention with moderate protein restriction reduces IGF-I and other metabolic modulators of BRCA penetrance. Methods: BRCA carriers, with or without a previous cancer, aged 18&ndash;70 years and without metastases were randomly assigned to an active dietary intervention group (IG) or to a control group (CG). The primary endpoint of the intervention was the IGF-I reduction. Results: 416 women (216 in the IG and 200 in the CG) concluded the six-month dietary intervention. The IG showed significantly lowered serum levels of IGF-I (&minus;11.3 ng/mL versus &minus;1.3 ng/mL, p = 0.02), weight (&minus;1.5 Kg versus &minus;0.5 Kg, p &lt; 0.001), waist circumference (&minus;2 cm versus &minus;0.7 cm, p = 0.01), hip circumference (&minus;1.6 cm versus &minus;0.5 cm, p = 0.01), total cholesterol (&minus;10.2 mg/dL versus &minus;3.6 mg/dL, p = 0.04) and triglycerides (&minus;8.7 mg/dL versus + 5.5 mg/dL, p = 0.01) with respect to the CG. Conclusions: A Mediterranean dietary intervention with moderate protein restriction is effective in reducing IGF-I and other potential modulators of BRCA penetrance

Image_1_Signatures of disease outcome severity in the intestinal fungal and bacterial microbiome of COVID-19 patients.pdf

BackgroundCOVID-19, whose causative pathogen is the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic in March 2020. The gastrointestinal tract is one of the targets of this virus, and mounting evidence suggests that gastrointestinal symptoms may contribute to disease severity. The gut–lung axis is involved in the immune response to SARS-CoV-2; therefore, we investigated whether COVID-19 patients’ bacterial and fungal gut microbiome composition was linked to disease clinical outcome.MethodsIn May 2020, we collected stool samples and patient records from 24 hospitalized patients with laboratory-confirmed SARS-CoV-2 infection. Fungal and bacterial gut microbiome was characterized by amplicon sequencing on the MiSeq, Illumina’s integrated next generation sequencing instrument. A cohort of 201 age- and sex-matched healthy volunteers from the project PRJNA661289 was used as a control group for the bacterial gut microbiota analysis.ResultsWe observed that female COVID-19 patients had a lower gut bacterial microbiota richness than male patients, which was consistent with a different latency in hospital admittance time between the two groups. Both sexes in the COVID-19 patient study group displayed multiple positive associations with opportunistic bacterial pathogens such as Enterococcus, Streptococcus, and Actinomyces. Of note, the Candida genus dominated the gut mycobiota of COVID-19 patients, and adult patients showed a higher intestinal fungal diversity than elderly patients. We found that Saccharomycetales unassigned fungal genera were positively associated with bacterial short-chain fatty acid (SCFA) producers and negatively associated with the proinflammatory genus Bilophila in COVID-19 patients, and we observed that none of the patients who harbored it were admitted to the high-intensity unit.ConclusionsCOVID-19 was associated with opportunistic bacterial pathogens, and Candida was the dominant fungal taxon in the intestine. Together, we found an association between commensal SCFA-producers and a fungal genus that was present in the intestines of patients who did not experience the most severe outcome of the disease. We believe that this taxon could have played a role in the disease outcome, and that further studies should be conducted to understand the role of fungi in gastrointestinal and health protection.</p